Acute aortic dissection associated with sleep apnea syndrome.

BACKGROUND: Sleep apnea syndrome (SAS) is an independent risk factor for hypertension which is a major risk factor for acute aortic dissection. The purposes of this study were to assess the prevalence of SAS in patients with acute aortic dissection, delineate the characteristics of patients who have acute aortic dissection with SAS. METHODS: Of 95 consecutive patients with acute aortic dissection, 13 had episodes of sleep apnea and nocturnal hypoxemia. A portable sleep monitoring system was used to assess sleep status in the 13 patients. RESULTS: The SAS-positive group consisted of 12 patients (12.6%), 8 with type A dissection and 4 with type B dissection. Age was significantly lower in the SAS-positive group (47.2 ± 8.5 years) than in the SAS-negative group (64.9 ± 10.3 years)(p <0.001). The male:female ratio was significantly higher in the SAS-positive group than in the SAS-negative group (p <0.001). The body mass index was significantly greater in the SAS-positive group than in the SAS-negative group (p <0.001). All 12 patients in the SAS-positive group had hypertension. CONCLUSIONS: Patients who have acute aortic dissection with SAS are characterized by being tall, fat, and relatively young men with hypertension. Sleep apnea syndrome may be a risk factor for acute aortic dissection in middle-aged men.

Synthesis of heterocyclic compounds via nucleophilic aroylation catalyzed by imidazolidenyl carbene.

Xanthones and acridones were synthesized from 3,4-difluoronitrobenzene and 2-fluorobenzaldehydes in two or three steps. The key step was nucleophilic aroylation catalyzed by imidazolidenyl carbene. The nucleophilic aroylation of 3,4-difluoronitrobenzene afforded 2,2'-difluoro-4-nitrobenzophenones. The cyclization of the difluorobenzophenones with O-nucleophile and N-nucleophile yielded 3-nitroxanthones and 3-nitroacridones, respectively. Indazole, quinolino[2,3-b]quinoxaline, and thianaphtho[2,3-b]quinoxaline derivatives were also synthesized via nucleophilic aroylation of 2,3-dichloroquinoxaline followed by cyclization with nucleophiles.

[A case of cT0N2M0 small cell lung cancer with Lambert-Eaton myasthenic syndrome].

We encountered a very rare case of cT0N2M0 small cell lung cancer (SCLC) with Lambert-Eaton myasthenic syndrome (LEMS). A 69-year-old man with a complaint of muscle weakness was admitted to our hospital. Although his chest radiograph on admission showed no abnormal findings, CT scanning detected a mediastinal lymphadenopathy. Also, 2-[18F]-2-fluorodeoxy-D-glucose position emission tomography (FDG-PET) revealed increased accumulation in the same portion in the mediastinum. A diagnosis of LEMS was made from the distinctive electromyogram (EMG) findings (waning and waxing phenomenon in response to low-and high-frequency repetitive stimulation, respectively) in combination with the increased serum level of a P/Q-type anti-voltage-gated calcium channel (VGCC) antibody. Subsequent histopathological diagnosis by mediastinoscopic resection of a paraaortic lymph node was small cell carcinoma. No distant metastasis was detected by MRI of the brain, abdominal CT scan or an FDG-PET. Eight courses of chemotherapy (carboplatin + etoposide) with radiotherapy of the mediastinum (for a total dose of 45 Gy) was performed. A decreased serum level of P/Q-type anti-VGCC antibody titers followed by marked improvement of neurological dysfunction (muscle weakness, gait disturbance and scanning speech) and of an EMG finding (a loss of waning phenomenon) was observed. A close relationship between reduction of the antibody titers and improvement of neurological symptoms after the therapy was noticed. It was suggested that monitoring the level of a P/Q-type anti-VGCC antibody titer in the serum is important for evaluating the efficacy of chemotherapy for LEMS associated with SCLC.

Effects of a high-monounsaturated fat diet on glucose and lipid metabolisms in normal and diabetic mice.

The beneficial effects of high-monounsaturated fat (high-MUFA) diets on diabetic patients have been reported, whereas studies concerning the effects on animals have been few. Although experiments on animals should be useful in elucidating underlying mechanisms, it is not clear even whether there are benefits of a high-MUFA diet in animals. This study examined the short-term effects of a high-MUFA diet on normal and genetically diabetic mice. The high-MUFA diet supplied 38% of the total calories as fat (26% from MUFA), while a regular diet was 13% fat (3% from MUFA). Normal C5 7BL/6J and diabetic C57BL/KsJ-db/db mice were fed either the regular or the high-MUFA diet for 1 wk. Serum glucose and lipid levels were then measured. In normal mice, hepatic triglyceride production was also compared between the two dietary groups using the Triton WR1339 method. An oral glucose tolerance test was conducted on the diabetic mice. After 1 wk of feeding to normal mice, the high-MUFA diet was seen to lower serum triglyceride levels and reduce hepatic triglyceride production in comparison with the regular diet; it is suggested that the lowering of triglyceride consists of mechanisms including reduced hepatic triglyceride production. When diabetic mice were fed the high-MUFA diet with a controlled caloric intake, the serum glucose levels lowered without an accompanying deterioration in lipid metabolism and the impaired glucose tolerance was ameliorated. This study demonstrates that a high-MUFA diet can lower serum triglyceride levels in normal mice and improve disorders of glucose metabolism in diabetic mice.

Oxygen administration improves the serum level of nitric oxide metabolites in patients with obstructive sleep apnea syndrome.

OBJECTIVES AND BACKGROUND: Nocturnal apnea and hypoxia are implicated in the pathogenesis of pulmonary and systemic hypertension in obstructive sleep apnea syndrome (OSAS). We have hypothesized that vasodilating factors including nitric oxide (NO) are affected by nocturnal apnea and hypoxia in patients with OSAS. METHOD: We examined the serum level of NO production in 24 patients with OSAS (mean age 54.2+/-7.9 years) and 24 age-matched control subjects (53.4+/-8.1 years) and tested the effects of oxygen administration on the production of NO in the patients. RESULTS: The serum level of nitrite/nitrates (NO(x)), which are stable metabolites of NO, was lower in patients with OSAS than in control subjects. Administration of 1-2 l/min of oxygen during night increased the patients' NO(x) level from 35.6+/-7.3 to 57.8+/-11.6 microM. Compressed air administration did not affect the NO(x) level in the patients. CONCLUSION: These results indicate that systemic NO production is impaired in OSAS patients, possibly due to nocturnal hypoxia.

Effects of oxygen administration on the circulating vascular endothelial growth factor (VEGF) levels in patients with obstructive sleep apnea syndrome.

OBJECTIVE: Repeated nocturnal hypoxia is implicated in the pathogenesis of cardiovascular complications in obstructive sleep apnea syndrome (OSAS). We hypothesized that circulating vascular endothelial growth factor (VEGF) levels are affected by nocturnal hypoxemia in patients with OSAS. METHODS: We examined the serum VEGF levels in patients with OSAS and in control subjects. We also tested the effects of oxygen or air administration on the subjects' VEGF levels. PATIENTS AND MATERIALS: Twenty-four OSAS patients (mean age 54.2 +/- 3.6 years) and 24 age-matched control subjects (53.2 +/- 3.6 years). Their serum samples were tested. RESULTS: Serum VEGF levels at 8:00 AM were significantly higher in OSAS patients than in controls (p<0.01). VEGF levels decreased from 515 +/- 31 (pg/ml) to 178 +/- 16 (pg/m) (p<0.01) in OSAS patients whose nocturnal hypoxemia was found to be improved by administration of 2 l/min of oxygen during the night. However, the administration of compressed air affected neither the VEGF level nor nocturnal oxygen desaturation in OSAS patients. CONCLUSION: These results indicate that circulating VEGF levels are elevated in OSAS patients, primarily due to nocturnal hypoxemia.

Nucleophilic acylation of arylfluorides catalyzed by imidazolidenyl carbene.

Imidazolidenyl carbene catalyzes nucleophilic acylation reaction of arylfluorides with electron withdrawing groups to give benzophenone derivatives.

[Questionnaire on the attitude of the physicians in educating the elderly patients with chronic obstructive pulmonary disease about smoking cessation].

Smoking status, the extent of recognition of the relationship between smoking and COPD, and actual nature of education for smoking cessation by physicians have not yet been fully elucidated. To investigate perceptions about education for smoking cessation in the elderly by physicians who work in the clinic, questionnaires were sent to the 1,012 physicians who belong to the Yokohama City Medical Association. Of these, 311 respond and their data (31%) were included in the analysis. The questionnaire included questions on the importance of smoking cessation in the elderly, on the perception about the relationship between smoking and various diseases, and actual education for smoking cessation. The smoking status of the physicians themselves was also investigated. The distribution of current smokers, ex-smokers, and non-smokers among the physicians was 13%, 33%, and 54%, respectively. Seventy-five percent of ex-smokers answered that their experience of smoking cessation influenced their patient education for smoking cessation, and 39% of smokers answered that their smoking status did not influence it. Only 53% of the physicians replied that they actually performed education for smoking cessation to the elderly, and 8% of them replied that they hardly perform any or do not perform it. Smoking cessation is thought to be the only way to prevent the development of COPD. However, only a half of physicians recognized the importance of smoking cessation for the treatment and control of COPD in the elderly. In addition, less than one third of physicians perform nicotine replacement therapy for smoking cessation. Enlightenment for physicians should be needed to make them perform education for smoking cessation more aggressively.

Analysis of exhaled nitric oxide by the helium bolus method.

STUDY OBJECTIVES: The precise anatomic sites contributing to exhaled nitric oxide (eNO) are still unknown. The present study was designed to analyze profiles of eNO by referring to the He exhalation curve and examining the effects of breath-holding and expiratory flow rates on eNO. PARTICIPANTS: Healthy volunteers and patients with stable asthma. MEASUREMENTS AND RESULTS We used the He bolus method of the closing volume, and simultaneously analyzed the concentrations of exhaled He and nitric oxide (NO). By referring to the He exhalation curve, the expired gas was divided into three parts: airway dead space (phase 1), a mixture of airway and alveolar gas (phase 2), and alveolar gas (phase 3 and phase 4). The eNO profiles showed a peak in phase 2 (peak eNO) and decreased gradually to a plateau in the latter half of phase 3 (plateau eNO). The levels of peak eNO were higher than those of plateau eNO in both normal subjects and asthmatic patients. Breath-holding increased levels of peak eNO 2.5-fold in both normal subjects and asthmatic patients, but it did not affect the levels of plateau eNO. The levels of peak eNO increased as the expiratory flow rate decreased, and the levels of plateau eNO showed a similar flow dependency. CONCLUSION: A peak value of eNO concentration profiles may directly express the production of NO in the airway.

[Chronic obstructive pulmonary disease (COPD) in the elderly: analysis from questionnaire about attitudes to the COPD guideline of the Japanese Respiratory Society and actual therapy for COPD used by physicians].

We have conducted a survey of attitudes to chronic obstructive pulmonary disease (COPD) in the elderly, a survey of attitudes to the COPD guideline prepared by the Japanese Respiratory Society, and a survey of the therapies actually used for this disease among physicians belonging to the Yokohama Medical Association. The results showed that most respondents thought that physicians, mainly except for respiratory physicians, miss the COPD patients because of failure to recognize COPD. The spread of the COPD guideline among physicians and the amount of therapy conducted according to this guideline were also insufficient. However, most physicians who know this guideline have used it well, and have also appreciated the contents. Thus, the results of our surveys suggested that this COPD guideline, with its step-by-step pharmacologic therapy, should be more widely disseminated, mainly among clinics and physicians that are not respiratory specialists. This would enable them to follow the guideline and improve their treatment of COPD. In addition, it was also supposed that the comprehensive respiratory rehabilitation should be more executed in the hospitals.

New mu-opioid receptor agonists with phenoxyacetic acid moiety.

New muq-opioid receptor (MOR) agonists containing 4-hydroxypiperidine, piperidine and piperazine moieties were synthesized and evaluated to find a peripheral opioid analgesic. Among the synthesized compounds, 12-[1-[3-(N,N-dimethylcarbamoyl)-3,3-diphenylpropyl]-4-hydroxypiperidin-4-yl]phenoxy]acetic acid (8: SS620) having phenoxyacetic acid and 4-hydroxypiperidine moieties showed the highest agonist potency on the MOR in an isolated guinea-pig ileum preparation, and it also had selectivity to the human MOR expressed in Chinese hamster ovary (CHO)-K1 cells compared with the same types of delta- and kappa-opioid receptors (DOR and KOR). In addition, compound 8 showed a 10 times more potent MOR agonist activity than loperamide. Furthermore, compound 8 showed a peripheral analgesic activity in vivo screening on rat.

Crystal and solution structures of photochromic spirobenzothiopyran. First full characterization of the meta-stable colored species.

Full elucidation for stable, colorless, and meta-stable colored structures of a new spirobenzothiopyran has been achieved both in the solid state and in a solution. 1',3',3'-Trimethyl-6-nitrospiro[(2H)-1-benzothiopyran-2,2'-indoline] with an ester group as a substituent at the 8-position of 1-sp shows photochromism. The blue-green colored species resulted from UV irradiation (365 nm) in one minute and spontaneously bleaches within one minute in acetone and methanol at 27 degrees C. UV exposure (365 nm) of 1-sp in methanol for 3 h at room temperature results in the growth of deep blue needlelike single crystals of the open form of spirobenzothiopyran, photomerocyanine 1-pmc, whose structures in the solid state and in solution were obtained unambiguously. The X-ray structural analysis of 1-pmc revealed the molecular structure of the zwitterionic photomerocyanine with s-trans,s-trans conformation. 1-pmc is soluble to polar solvents and thermally returns to 1-sp. In the DMSO solution, 1-pmc is found to return slowly to 1-sp (1-pmc gave only 18% of 1-sp for 30 min at 22 degrees C). The detailed NMR studies in DMSO-d(6) including COSY and NOE techniques as well as isotope labeling of the compound showed the structure with s-trans,s-cis conformation in a solution.